The notion that schizophrenia has an important autoimmune component has been around for several decades, but has not previously been subjected to analysis by the most sensitive, modern techniques. We have hypothesized that early (perinatal) tolerance to viruses, which use the receptor molecule to gain cellular entry, causes this autoimmunity. We have developed a simple sensitive assay for detecting antibodies directed against human brain found in sera of schizophrenic patients and controls. We are now subjecting human brain membrane receptors to either native or denaturing solubilization conditions and separation by polyacrylamide gel electrophoresis (PAGE). After visualization by antiserum or CSF from patients and controls, we hope to identify the specific brain antigens against which schizophrenics have generated antibodies.